Mycobacteria are slow-growing aerobic bacteria characterized by their surface glycolipids, and by the high G-C content of their DNA (&gt;63%). Organisms of the genus Mycobacterium include more than 30 well-characterized members and many that are as yet unclassified. Most are not pathogenic for humans, but among the mycobacteria are the etiologic agents for leprosy (M. leprae) and for tuberculosis (M. tuberculosis), the leading cause of death in the world from an infectious disease (Bloom, B. R. and Murray, C. J. L., Science, 257:1055-1064 (1992)).
It has been estimated that as much as one third of the population of the world is infected with M. tuberculosis, and that tuberculosis (TB) is responsible for one in four avoidable adult deaths in developing countries (Murray, C. J. L. et al., pp. 233-259 In Disease Control Priorities in Developing Countries, D. T. Jamison et al., Eds. (Oxford Univ. Press, New York, 1993). Since the 1980s the number of new cases of TB infections has steadily increased both in the US and in Europe. Individuals infected with the human immunodeficiency virus (HIV) are particularly susceptible to infection with M. tuberculosis, a growing problem that threatens the control of the spread of tuberculosis.
Infection caused by drug-sensitive strains of M. tuberculosis has been successfully treated by using a combination of isoniazid, rifampicin and pyrazinamide. However, in cities worldwide, the emergence of multidrug resistant isolates of M. tuberculosis is becoming alarming. The fatality rate for drug-resistant TB is 50%. According to the World Health Organization, almost 20% of the isolates tested in New York City in 1992 were resistant to both isoniazid and rifampicin.
It would be a great advantage in the control of diseases caused by the Mycobacteria to expand the number of target molecules whose function could be inhibited by antibiotic agents.